VHL and cancer: Although HIF-1 signalling has been associated with increased mortality of most human cancers through multiple aspects of the pro-tumorigenic process including angiogenesis, tumour growth, metastasis, chemoresistance and radioresistance16, 17, 18, recent studies reported that HIF-1α could act as a tumour suppressor in certain cancers such as VHL-null renal cell carcinoma where HIF-2α functions as a dominant oncogenic driver.